Canada Research Chair in Prevention of Dementia - Tier 1
​Pfizer Chair in Dementia Research

Director, Centre for Studies on Prevention of Alzheimer’s Disease (StoP-AD), Douglas Research CentreFull Professor, Department of Psychiatry, McGill University

Prevention of Alzheimer’s disease

Research Summary

The research program of the Centre for Studies on Prevention of Alzheimer’s Disease (StoP-AD) seeks treatments that can attenuate the trajectories of a host of cognitive, chemical, neuroimaging, or sensori-neural biomarkers of pre-symptomatic Alzheimer’s disease. As of May, 2015, participants include 270 individuals who are aged 60+ and have a parental history of Alzheimer's dementia, placing them at substantially exaggerated risk of subsequent dementia.

Current studies include:

- a two-year randomized, placebo-controlled double-masked trial of low dose naproxen sodium (N = 150)
- (in preparation) a two-year proof-of-concept trial of the cholesterol-lowering drug probucol, which is believed to induce synthesis of apolipoprotein E to mimic effects of the low-risk alleles of APOE, the major genetic risk factor for Alzheimer's disease.
- a longitudinal cohort natural history study of the same biomarkers to identify optimal endpoints for trials of potential preventive agents
- development of methods for combining multiple independent biomarkers of pre-symptomatic Alzheimer's disease into simple summary measures that can facilitate read-out of clinical trials in pre-symptomatic disease.

Dr. Breitner has devoted his career to investigation of factors that modify the risk of Alzheimer’s dementia (AD). Initial studies on familial aggregation used new methods to demonstrate that AD (including late-onset disease) is a strongly familial disorder. To investigate the role of genetic vs. environmental factors responsible for this familial aggregation, Dr. Breitner initiated a large, population-based twin study that is still ongoing with over 300 affected pairs now identified. The twin studies suggested a substantial adult environmental contribution to AD susceptibility, and a co-twin control study found that non-steroidal anti-inflammatory drugs (NSAIDs) were used more frequently by the unaffected member of such pairs. This finding was reproduced many times in relatively young samples (it does not seem to hold in persons older than age 80 years). Dr. Breitner therefore led efforts to conduct a large randomized trial (ADAPT) of two different NSAIDs in healthy elderly with a strong family history of AD, who were accordingly at increased risk. ADAPT encountered substantial difficulties because of safety concerns about sustained use of NSAIDs (especially newer “coxib” agents) by older people, and its treatments were therefore terminated in 2005, when most participants had been on treatment for only two years. Participants were followed closely for another 18 months, during which time ADAPT collected biosamples (including cerebrospinal fluid, or CSF) from those remaining under observation. During the follow-up interval, participants treated earlier with naproxen showed reduced incidence of AD (compared with those given placebo). They also had a biochemical profile in their CSF that suggested diminished ongoing AD neurodegenerative change. The latter observation established a precedent for the possible use of biomarkers as endpoints for intervention trials in the pre-symptomatic stages of Alzheimer’s disease. Dr. Breitner (and others) recognized the potential for this sort of research as a promising pathway to the prevention of AD.

Dr. Breitner was recruited by the Douglas Mental Health University Institute and McGill University to lead a new Centre for Studies on Prevention of Alzheimer’s Dementia (StoP-AD) at the Douglas. The Centre’s research program evaluates whether treatments can reduce cognitive, chemical, neuroimaging or sensorineural biomarkers that may track the development of Alzheimer’s disease in its pre-symptomatic stages.

Dr. Breitner has authored over 200 publications (H-index 64 per Web of Science) and is known as an outstanding teacher. He has mentored more than 15 doctoral and post-doctoral students who have gone on to hold full-time academic appointments.

Prizes & Distinctions

Canada Research Chair in Prevention of Dementia
Pfizer Chair in Dementia Research
Fellow (emeritus), American College of Neuropsychopharmacology
Fellow, American Psychopathological Association